The main objective of this project is to study the role played by histamine, through its action on H1 and H2 receptors, as well as through the release of prostaglandins on the bronchial tonus of normal, asthmatic and bronchitic subjects. Special attention will be given to endogenous histamine. Endogenous histamine's role in resting bronchial tonus and in acute bronchospastic events will be studied with the aid of inhaled chlorpheniramine, an H1 blocker, and iv cimetidine, an H2 blocker. In some experiments, for technical reasons, exogenous histamine will be used in order to mimic the effects of endogenous histamine. Initially, preparatory experiments will define the antihistaminic activity of various doses of inhaled and i.v. chlorpheniramine, their anticholinergic activity as well as the effects of a bronchodialating dose of the same drug on various physiologic measurements of respiration. In the main part of the study, we will determine; a) whether the bronchial hyperreactivity to histamine is due to a partial contraction of bronchial muscle (resting bronchoconstriction), or to an increased affinity of the H1 receptor for histamine; b) the role of endogenous histamine in the resting tonus of the bronchial muscle as well as in the acute bronchospasm produced by allergens, irritants, exercise and aspirin; c) the time course and mechanics of bronchial relaxation following histamine contraction; d) the possible modulating effect of endogenous histamine acting on H2 receptors influencing the release of prostaglandins; e) the physiological significance of prostaglandins released by inhaled histamine and allergen. This new and basic physiological and pharmacological data will improve the understanding of the mechanisms involved in bronchial hyperactivity to histamine in the resting bronchial tonus of asthma and chronic bronchitis, and in various forms of acute bronchospasm. The results will also determine to what extent the H1 blockers can be useful in the therapy of these diseases.